The stability of lower genital tract (LGT) microbiota correlates with reproductive system function and in vitro fertilization and frozen embryo transfer outcomes in women with polycystic ovarian syndrome

We previously found that the lower genital tract (LGT) microbiota of polycystic ovarian syndrome (PCOS) women has altered when compared to healthy reproductive-aged women, however whether this alternation will have an impact on the reproductive system function and pregnancy outcomes of PCOS patients have not yet been identified. Between 2018 and 2021, we totally enrolled 191 reproductive-aged women in three independent case-control studies, 209 vaginal and 209 cervical swabs, and 9 cervical epithelial cells samples were collected from the study subjects. Firstly, we analyzed the correlation between LGT flora and clinical characteristics of 97 women (containing 47 PCOS patients and 50 control reproductive-aged women), canonical correspondence analysis (CCA) showed that LH/FSH ratio was the most relevant factor that was related to the dominant genera in women with PCOS (r2=0.233, p=0.001), and menstrual cycle frequency was also strongly related to the LGT organisms (r2=0.116, p=0.005). Next, through analysis of 72 PCOS patients who were underwent IVF-FET therapy, the FET outcome in PNB group (PCOS with relative abundance of Lactobacillus ≥50%, n=57) was significant better than PDB group(PCOS patients with relative abundance of Lactobacillus <50%, n=15). Further, we randomly selected nine reproductive-aged PCOS patients (approximately half of them had altered LGT microbiota: Lactobacillus spp. ≤50%, n=5) and simultaneously collected both LGT swabs and cervical epithelial cells from them. By synchronization analysis of RNA sequencing of the cervical epithelial cells and 16S rRNA sequencing of the microbes, we found that the gene expression profiles of the cells significantly differed between the PDB (PCOS patients with relative abundance of Lactobacillus <50%, n=4) and PNB (PCOS with relative abundance of Lactobacillus ≥50%, n=5) groups. Above all, we systematically elucidate the potential relationship between LGT microbiota with the reproductive system function and IVF-FET outcomes in PCOS patients. Importance polycystic ovarian syndrome (PCOS) women always suffered from poor pregnancy outcome: high incidence of abortion, preterm-birth, and premature rupture of membranes. Although some patients have improved their reproductive outcomes through assisted reproductive technology, the risk of early clinical pregnancy loss for PCOS patients after IVF treatment still ranges from 12% to 48%. As we previously found that the LGT flora of PCOS women had significant altered when compared with healthy parallel group, and more evidence showed that the genital tract microbiota may have a critical role in the process of embryo implantation and development, here we used multiple study groups to explore the potential relationship between LGT microbiota with reproductive system function and FET outcome in PCOS patients in this study. Our findings provide a new perspective for exploring novel therapy to improve the reproductive outcomes of PCOS patients.